6fqk
From Proteopedia
(Difference between revisions)
| (One intermediate revision not shown.) | |||
| Line 3: | Line 3: | ||
<StructureSection load='6fqk' size='340' side='right'caption='[[6fqk]], [[Resolution|resolution]] 1.98Å' scene=''> | <StructureSection load='6fqk' size='340' side='right'caption='[[6fqk]], [[Resolution|resolution]] 1.98Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6fqk]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FQK OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6fqk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FQK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FQK FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZK1:{[7-MORPHOLIN-4-YL-2,3-DIOXO-6-(TRIFLUOROMETHYL)-3,4-DIHYDROQUINOXALIN-1(2H)-YL]METHYL}PHOSPHONIC+ACID'>ZK1</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9801044Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZK1:{[7-MORPHOLIN-4-YL-2,3-DIOXO-6-(TRIFLUOROMETHYL)-3,4-DIHYDROQUINOXALIN-1(2H)-YL]METHYL}PHOSPHONIC+ACID'>ZK1</scene></td></tr> |
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6fqk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fqk OCA], [https://pdbe.org/6fqk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fqk RCSB], [https://www.ebi.ac.uk/pdbsum/6fqk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fqk ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/GRIA2_RAT GRIA2_RAT] Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.<ref>PMID:9351977</ref> <ref>PMID:19265014</ref> <ref>PMID:21172611</ref> <ref>PMID:12501192</ref> <ref>PMID:12015593</ref> <ref>PMID:12872125</ref> <ref>PMID:12730367</ref> <ref>PMID:16192394</ref> <ref>PMID:15591246</ref> <ref>PMID:17018279</ref> <ref>PMID:16483599</ref> <ref>PMID:19946266</ref> <ref>PMID:21317873</ref> <ref>PMID:21846932</ref> |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Desensitization is a canonical property of ligand-gated ion channels, causing progressive current decline in the continued presence of agonist. AMPA-type glutamate receptors (AMPARs), which mediate fast excitatory signaling throughout the brain, exhibit profound desensitization. Recent cryo-EM studies of AMPAR assemblies show their ion channels to be closed in the desensitized state. Here we present evidence that homomeric Q/R-edited AMPARs still allow ions to flow when the receptors are desensitized. GluA2(R) expressed alone, or with auxiliary subunits (gamma-2, gamma-8 or GSG1L), generates large fractional steady-state currents and anomalous current-variance relationships. Our results from fluctuation analysis, single-channel recording, and kinetic modeling, suggest that the steady-state current is mediated predominantly by conducting desensitized receptors. When combined with crystallography this unique functional readout of a hitherto silent state enabled us to examine cross-linked cysteine mutants to probe the conformation of the desensitized ligand binding domain of functioning AMPAR complexes. | ||
| + | |||
| + | Homomeric GluA2(R) AMPA receptors can conduct when desensitized.,Coombs ID, Soto D, McGee TP, Gold MG, Farrant M, Cull-Candy SG Nat Commun. 2019 Sep 20;10(1):4312. doi: 10.1038/s41467-019-12280-9. PMID:31541113<ref>PMID:31541113</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6fqk" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 14: | Line 27: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Coombs | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Cull-Candy | + | [[Category: Coombs ID]] |
| - | [[Category: Farrant | + | [[Category: Cull-Candy SG]] |
| - | [[Category: Gold | + | [[Category: Farrant MF]] |
| - | [[Category: Soto | + | [[Category: Gold MG]] |
| - | + | [[Category: Soto D]] | |
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
Current revision
GluA2(flop) S729C ligand binding core dimer bound to ZK200775 at 1.98 Angstrom resolution
| |||||||||||
